Effect of Tenapanor on the Metagenomics and Metabolomics of Patients With Irritable Bowel Syndrome With Constipation

NCT05995899 | Completed Phase 4 FDA Drug

• 1 other identifier: 2023P001911
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to better understand how tenapanor affects the metagenomics and metabolomics of patients with irritable bowel syndrome with constipation (IBS-C). Tenapanor is the newest FDA-approved agent for IBS-C. It is a small molecule that inhibits the NHE3 receptor, leading to impaired sodium and water absorption in the intestine. Previous clinical trials comparing tenapanor to placebo showed that a 50 mg dose of tenapanor led to increased bowel movements and decreased abdominal pain. This study consists of an 8-week treatment period in which subjects will ingest one capsule of tenapanor (50 mg per dose), twice daily, and send in stool samples following 4 weeks and 8 weeks of treatment.

Conditions

IBS - Irritable Bowel Syndrome; IBS

Outcome Measures

Primary Outcomes (2)

• Measuring metagenomics of stool samples using whole genome shotgun sequencing (WGS)

  Sequence-based microbial community surveys will be carried out by whole genome shotgun sequencing (WGS) at the Broad Institute using their established sequencing and analysis pipeline for the Illumina HiSeq2000 platform used in Human Microbiome Project (HMP) to characterize rare taxa and understand relationships between community membership and function. Composition analysis of metagenome will be performed using the read-based bioinformatics analysis suite. Functional genomic profiles, detailed species-specific reconstruction of microbial metabolic pathways, their complement of gene orthologs, taxonomic distributions, and abundances will be generated with HUMAnN2. This will provide taxon-specific profiles of UniRef orthologous gene families, MetCyc, UniPathway, and KEGG pathways to survey microbial community metabolite production potential in each metagenome according to tenapanor use.

  Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.

• Measuring metabolomics of stool samples using the DiscoveryHD4TM Platform

  Stool samples will also undergo metabolomics profiling at Metabolon Inc using the DiscoveryHD4TM Platform, a comprehensive and well-validated high-throughput metabolomics platform available for clinical and research use. Metabolites are identified by automated comparison of the ion features in the experimental samples to a reference library of \~8,000 chemical standard entries that include retention time, molecular weight (m/z), preferred adducts, in-source fragments and MS spectra, and they are visually curated for quality control using Metabolon software.

  Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.

Study Arms (1)

Patients with IBS-C

EXPERIMENTAL

Drug: Tenapanor

Interventions

Tenapanor DRUG

IBS-C patients will ingest one capsule of tenapanor (50 mg per dose), twice daily, before breakfast and dinner for a total of 8 weeks

Patients with IBS-C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-75 years old
• BMI \>18.5 and \<35 kg/m2
• Rome IV criteria for IBS-C for at least 6 months
• Compliant with baseline stool submission prior to initiation of medication
• Ability to follow verbal and written instructions
• Ability to record daily bowel habits, including frequency, stool consistency (BSFS), and symptom severity
• Willingness to avoid major dietary changes and use of probiotics during the study period
• Informed consent form signed by the subjects

You may not qualify if:

• History of loose stools
• History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel syndrome (IBS-M)
• Non-compliance with baseline stool submission
• Previous use of tenapanor
• GI motility obstruction or GI tract structural abnormality
• Current use of prescribed or illicit opioids
• History of pelvic floor dysfunction
• Need for manual maneuvers in order to achieve a BM
• History of GI lumen surgery at any time or other GI or abdominal operations within 60 days prior to entry into the study
• History of high-dose stimulative or cathartic laxative abuse as judged by investigator team
• Severe IBS-C as judged by the investigator
• Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study
• Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis
• BMI of \<18.5 or \>35 kg/m2
• Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) or lactation

Sponsors & Collaborators

• Ardelyx: collaborator
• Kyle Staller, MD, MPH: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

tenapanor

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Gastroenterology Physician

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 16, 2023
• Study Start: February 6, 2024
• Primary Completion: December 17, 2025
• Study Completion: December 17, 2025
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)